Ignite Creation Date:
2024-10-26 @ 3:35 PM
Last Modification Date:
2024-10-26 @ 3:35 PM
Study NCT ID:
NCT06503120
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-07-02
Brief Title:
Nutritional Education Program for Metabolic Dysfunction-Associated Steatotic Liver Disease MASLD
Sponsor:
None
Organization:
None
Study Overview
Official Title:
A Brief Structured Online Nutritional Education Program is Effective in the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease Management A Randomized Controlled Trial
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Study Summary Title Mediterranean Diet Intervention for Metabolic Dysfunction-Associated Steatotic Liver Disease MASLD A Randomized Controlled Trial
Aims
Primary Aim Assess the impact of an iso-calorie Mediterranean diet compared to standard care on intrahepatic fat in MASLD patients
Secondary Aims Evaluate the effects on liver function tests lipid profiles HbA1c and insulin resistance homeostatic model assessment of insulin resistance HOMA-IR noninvasive assessment of hepatic fibrosis with transient elastography by Fibroscan Framingham Risk Score FRS serum metabolites quality of life QoL compliance and stool microbiome
Study Design
Type 12-week prospective two parallel-group randomized controlled trial
Participants MASLD patients with 5 hepatic steatosis diagnosed by MRI-PDFF randomized into two groups Mediterranean diet intervention and standard care
Randomization
Method Computer-generated random numbers 11 allocation
Blinding Radiologists and statisticians blinded to treatment assignment
Intervention
Mediterranean Diet Group Specific dietary guidelines provided
Standard Care Group Simple lifestyle advice
Compliance
Monitored through standardized questionnaires and T-MEDAS at each visit
Assessments
Reduction of hepatic triglyceride content by MRI-PDFF at baseline and week 12
Conclusion This trial aims to determine the effectiveness of a Mediterranean diet in reducing intrahepatic fat and improving related metabolic and microbiome parameters in MASLD patients compared to standard care
Aims
Primary Aim Assess the impact of an iso-calorie Mediterranean diet compared to standard care on intrahepatic fat in MASLD patients
Secondary Aims Evaluate the effects on liver function tests lipid profiles HbA1c and insulin resistance homeostatic model assessment of insulin resistance HOMA-IR noninvasive assessment of hepatic fibrosis with transient elastography by Fibroscan Framingham Risk Score FRS serum metabolites quality of life QoL compliance and stool microbiome
Study Design
Type 12-week prospective two parallel-group randomized controlled trial
Participants MASLD patients with 5 hepatic steatosis diagnosed by MRI-PDFF randomized into two groups Mediterranean diet intervention and standard care
Randomization
Method Computer-generated random numbers 11 allocation
Blinding Radiologists and statisticians blinded to treatment assignment
Intervention
Mediterranean Diet Group Specific dietary guidelines provided
Standard Care Group Simple lifestyle advice
Compliance
Monitored through standardized questionnaires and T-MEDAS at each visit
Assessments
Reduction of hepatic triglyceride content by MRI-PDFF at baseline and week 12
Conclusion This trial aims to determine the effectiveness of a Mediterranean diet in reducing intrahepatic fat and improving related metabolic and microbiome parameters in MASLD patients compared to standard care
Detailed Description:
Subject selection
1 Screening of potential subjects at the out-patient clinic Consecutive patients attending the hepatology of the Taichung Veterans General Hospital will be screened Patients with features of fatty liver on ultrasound scan bright echotexture reduced ultrasound penetrance and blurred vascular markings magnetic resonance imaging will be screened after signing informed written consent The screening procedure is described in section Screening
Randomization Subjects meeting the inclusion and exclusion criteria will be randomized 11 to participate in an iso-calorie Mediterranean diet MD intervention or to receive simple lifestyle advice alone Randomization is carried out through the use of computer-generated list of random numbers Treatment assignment will be revealed in sealed envelopes
Trial treatments
1 Blinding Radiologists who evaluate the magnetic resonance image and physicians doing transient elastography by Fibroscan will be blinded to the treatment assignment
2 Dietary intervention program
Nutritionist Education Process
1 Utilize the Taiwan version of the Mediterranean Diet Adherence Screener MEDAS validated by our team as shown below dividing its 14 items into seven question groups Based on previous studies common scoring patterns among Taiwanese people and factors likely to change with food provision eg olive oil and nuts the priority sequence for recommendations is as follows
I Olive oil-related Derived from items 12 II Protein sources Items 591013 III Nuts Item 12 IV Fruits and vegetables Items 34 V Sugary drinks and sweets Items 711 VI Cream Item 6 VII Quality of carbohydrates Items 814
2 Before each educational session collect the participants MEDAS score and a three-day photographic food diary Based on this data determine the two to three question groups where the participant should prioritize improvement
3 Conduct online educational sessions at Weeks 0 3 6 and 9 lasting 10 to 15 minutes each focusing on the relevant question groups Tailor the education to the participants dietary habits such as the frequency and type of dining out and provide two to three graphic-based suggestions after each session highlighting key points for both dining out and home cooking
4 For the intake of olive oil we recommend using a 15mL measuring cup or tablespoon and suggest adding it to vegetable juice or drizzling it over vegetables We intend to start with 30mL of olive oil and gradually increase it if the patients tolerate well after 3 to 6 weeks
5 The ultimate goal is to increase the MEDAS score by more than five points within 12 weeks without calorie restriction
6 After the initial education session provide participants with a common Q and A sheet online based on the dietary advice given We also provide education materials a food-group list specifying preferred choices and approximate numbers and size of servings to consume per day
7 Conduct a 3-minute telephone interview within one week after each educational session to understand the participants adherence and the challenges they face
8 The investigators will provide an adequate amount of mixed nuts 15g per day and extra virgin olive oil 60mL per day The investigators will also provide an electronic scale
9 At the Week 0 and Week 6 follow-up appointments lunch will be provided
c Standard care Simple lifestyle advice A 10-minute talk on the epidemiology of MASLD and balanced diet resembling routine clinical practice
d Compliance At each scheduled visit subjects completed a standardized compliance questionnaire and Taiwan version of the Mediterranean Diet Adherence Screener MEDAS
e Exercise Subjects were advised to maintain their usual level of activity for the duration of the intervention f Accessibility All subjects received equivalent intensity of care in terms of opportunities for contact
Trial procedures
1 Screening
Screening will be performed for suitability of inclusion at the original clinic Informed consent will be obtained prior to all screening assessment After obtaining informed consent the following screening will be performed
Verify inclusionexclusion criteria
Record medical and medication history from the national insurance database
Physical examination including subjects height weight waist circumference hip circumference
Clinical laboratory tests including complete blood count prothrombin time liver function renal function HBsAg anti-HCV ANA
Items used for screening other liver diseases such as viral hepatitis autoimmune or cholestatic liver diseases and Wilsons disease that have been checked within the past year do not need to be rechecked during the screening process
Arrange Magnetic Resonance Spectrum MRS and Magnetic Resonance Imaging-Proton Density Fat Fraction MRI-PDFF
During the initial screening the investigators hold a formal outpatient session to outline the benefits of the Mediterranean diet presenting current evidence and inquiring if patients are interested in dietary treatment Physicians also evaluate participants acceptance of olive oil during the session by serving a raw salad with olive oil dressing
2 Baseline randomization visit Randomization will be performed after the above procedure
3 Procedures and assessments after randomization The questionnaires to be obtained include a Taiwanese version of the Mediterranean Diet Adherence Screener T-MEDAS a validated food frequency questionnaire the WHO Quality of Life WHO QOL questionnaire and the International Physical Activity Questionnaire
Clinical lab tests include liver function renal function aspartate aminotransferase gamma-glutamyl transferase fasting glucose HbA1c lipid profile HDL-cholesterol LDL-cholesterol and insulin serum metabolites stool microbiome If the screening is within four weeks a repeat blood test will not be required
Subjects will obtain a 24-hour telephone to report any serious adverse events between the visits
Sample size calculation In a previous trial 25 to 324 relative reduction in hepatic steatosis was achieved by Mediterranean diet for 12 weeks Another trial showed 39 relative reduction in hepatic steatosis in those having Mediterranean diet for 12 weeks A previous NAFLD study performed in Hong Kong with a non-obese population the mean intrahepatic fat was 110 567 Assuming that 28 relative reduction could be achieved in patients with Mediterranean diet intervention group The investigators aimed to recruit 88 subjects Allowing for 10 dropout this would provide 78 subjects per treatment group to detect diet-induced differences based on a significance level of 5 power of at least 80
Statistical analysis
a Data analysis
a-1 Intention-to-treat population The intention-to-treat population includes all participants who have attended the randomization The intention-to-treat population will be used for the endpoint analysis Patients who withdraw from the study or refuse to have follow-up will be considered to have stationary intrahepatic fat
1 2 Per-protocol population Those who have at least two visits including the week 12 visit are included for the per-protocol analysis
a-3 Demographic data Randomized subjects will be included in the demographics characteristics analysis and the number and percentage was used for categorical variables while mean standard deviation was used for continuous variables
1 4 Analysis of the primary endpoint Analysis of the primary endpoint will be summarized by the difference between the intrahepatic fat levels for each treatment arm The null and alternative hypotheses are no difference between the intra-hepatic fat levels in each treatment arm at week 12
Comparison of the primary endpoint between the treatment groups will be performed using repeated measures analysis of covariance ANCOVA to examine differences in outcomes between diet groups at week 12 after adjusting for baseline values Statistical differences within groups were analyzed by paired t tests Testing will be performed at a 5 significance level
b Secondary endpoints Comparison of the treatment groups for all categorical secondary endpoints will be performed on the intention-to-treat population A two-sided Students t test will be used for continuous secondary endpoints Testing will be performed at a 5 significance level Chi-square test or Fisher exact test will be used for continuous variable Testing for treatment group differences will be performed at a 5 significance level
d Safety analysis All participants in the intention-to-treat population will be analyzed for vital signs laboratory data and treatment related adverse events
1 Screening of potential subjects at the out-patient clinic Consecutive patients attending the hepatology of the Taichung Veterans General Hospital will be screened Patients with features of fatty liver on ultrasound scan bright echotexture reduced ultrasound penetrance and blurred vascular markings magnetic resonance imaging will be screened after signing informed written consent The screening procedure is described in section Screening
Randomization Subjects meeting the inclusion and exclusion criteria will be randomized 11 to participate in an iso-calorie Mediterranean diet MD intervention or to receive simple lifestyle advice alone Randomization is carried out through the use of computer-generated list of random numbers Treatment assignment will be revealed in sealed envelopes
Trial treatments
1 Blinding Radiologists who evaluate the magnetic resonance image and physicians doing transient elastography by Fibroscan will be blinded to the treatment assignment
2 Dietary intervention program
Nutritionist Education Process
1 Utilize the Taiwan version of the Mediterranean Diet Adherence Screener MEDAS validated by our team as shown below dividing its 14 items into seven question groups Based on previous studies common scoring patterns among Taiwanese people and factors likely to change with food provision eg olive oil and nuts the priority sequence for recommendations is as follows
I Olive oil-related Derived from items 12 II Protein sources Items 591013 III Nuts Item 12 IV Fruits and vegetables Items 34 V Sugary drinks and sweets Items 711 VI Cream Item 6 VII Quality of carbohydrates Items 814
2 Before each educational session collect the participants MEDAS score and a three-day photographic food diary Based on this data determine the two to three question groups where the participant should prioritize improvement
3 Conduct online educational sessions at Weeks 0 3 6 and 9 lasting 10 to 15 minutes each focusing on the relevant question groups Tailor the education to the participants dietary habits such as the frequency and type of dining out and provide two to three graphic-based suggestions after each session highlighting key points for both dining out and home cooking
4 For the intake of olive oil we recommend using a 15mL measuring cup or tablespoon and suggest adding it to vegetable juice or drizzling it over vegetables We intend to start with 30mL of olive oil and gradually increase it if the patients tolerate well after 3 to 6 weeks
5 The ultimate goal is to increase the MEDAS score by more than five points within 12 weeks without calorie restriction
6 After the initial education session provide participants with a common Q and A sheet online based on the dietary advice given We also provide education materials a food-group list specifying preferred choices and approximate numbers and size of servings to consume per day
7 Conduct a 3-minute telephone interview within one week after each educational session to understand the participants adherence and the challenges they face
8 The investigators will provide an adequate amount of mixed nuts 15g per day and extra virgin olive oil 60mL per day The investigators will also provide an electronic scale
9 At the Week 0 and Week 6 follow-up appointments lunch will be provided
c Standard care Simple lifestyle advice A 10-minute talk on the epidemiology of MASLD and balanced diet resembling routine clinical practice
d Compliance At each scheduled visit subjects completed a standardized compliance questionnaire and Taiwan version of the Mediterranean Diet Adherence Screener MEDAS
e Exercise Subjects were advised to maintain their usual level of activity for the duration of the intervention f Accessibility All subjects received equivalent intensity of care in terms of opportunities for contact
Trial procedures
1 Screening
Screening will be performed for suitability of inclusion at the original clinic Informed consent will be obtained prior to all screening assessment After obtaining informed consent the following screening will be performed
Verify inclusionexclusion criteria
Record medical and medication history from the national insurance database
Physical examination including subjects height weight waist circumference hip circumference
Clinical laboratory tests including complete blood count prothrombin time liver function renal function HBsAg anti-HCV ANA
Items used for screening other liver diseases such as viral hepatitis autoimmune or cholestatic liver diseases and Wilsons disease that have been checked within the past year do not need to be rechecked during the screening process
Arrange Magnetic Resonance Spectrum MRS and Magnetic Resonance Imaging-Proton Density Fat Fraction MRI-PDFF
During the initial screening the investigators hold a formal outpatient session to outline the benefits of the Mediterranean diet presenting current evidence and inquiring if patients are interested in dietary treatment Physicians also evaluate participants acceptance of olive oil during the session by serving a raw salad with olive oil dressing
2 Baseline randomization visit Randomization will be performed after the above procedure
3 Procedures and assessments after randomization The questionnaires to be obtained include a Taiwanese version of the Mediterranean Diet Adherence Screener T-MEDAS a validated food frequency questionnaire the WHO Quality of Life WHO QOL questionnaire and the International Physical Activity Questionnaire
Clinical lab tests include liver function renal function aspartate aminotransferase gamma-glutamyl transferase fasting glucose HbA1c lipid profile HDL-cholesterol LDL-cholesterol and insulin serum metabolites stool microbiome If the screening is within four weeks a repeat blood test will not be required
Subjects will obtain a 24-hour telephone to report any serious adverse events between the visits
Sample size calculation In a previous trial 25 to 324 relative reduction in hepatic steatosis was achieved by Mediterranean diet for 12 weeks Another trial showed 39 relative reduction in hepatic steatosis in those having Mediterranean diet for 12 weeks A previous NAFLD study performed in Hong Kong with a non-obese population the mean intrahepatic fat was 110 567 Assuming that 28 relative reduction could be achieved in patients with Mediterranean diet intervention group The investigators aimed to recruit 88 subjects Allowing for 10 dropout this would provide 78 subjects per treatment group to detect diet-induced differences based on a significance level of 5 power of at least 80
Statistical analysis
a Data analysis
a-1 Intention-to-treat population The intention-to-treat population includes all participants who have attended the randomization The intention-to-treat population will be used for the endpoint analysis Patients who withdraw from the study or refuse to have follow-up will be considered to have stationary intrahepatic fat
1 2 Per-protocol population Those who have at least two visits including the week 12 visit are included for the per-protocol analysis
a-3 Demographic data Randomized subjects will be included in the demographics characteristics analysis and the number and percentage was used for categorical variables while mean standard deviation was used for continuous variables
1 4 Analysis of the primary endpoint Analysis of the primary endpoint will be summarized by the difference between the intrahepatic fat levels for each treatment arm The null and alternative hypotheses are no difference between the intra-hepatic fat levels in each treatment arm at week 12
Comparison of the primary endpoint between the treatment groups will be performed using repeated measures analysis of covariance ANCOVA to examine differences in outcomes between diet groups at week 12 after adjusting for baseline values Statistical differences within groups were analyzed by paired t tests Testing will be performed at a 5 significance level
b Secondary endpoints Comparison of the treatment groups for all categorical secondary endpoints will be performed on the intention-to-treat population A two-sided Students t test will be used for continuous secondary endpoints Testing will be performed at a 5 significance level Chi-square test or Fisher exact test will be used for continuous variable Testing for treatment group differences will be performed at a 5 significance level
d Safety analysis All participants in the intention-to-treat population will be analyzed for vital signs laboratory data and treatment related adverse events
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None